Death In Hypertrophic Cardiomyopathy Research Articles

Adverse prognostic implications of increased left ventricular force in hypertrophic cardiomyopathy

Abstract Background The left ventricular (LV) force, also known as elastance, serves as a load-independent indicator of contractility and can be noninvasively assessed through echocardiography. In hypertrophic cardiomyopathy (HCM), the heightened presence of the active state of myosin heads results in an increased LV force. Purpose To assess the prognostic value of increased LV elastance at rest in patients with HCM. Methods We enrolled 1420 HCM patients (age 50±16 years, 907 males, 64%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 10 quality-controlled labs from 7 countries. TTE assessment included peak left ventricular outflow tract gradient (LVOTG), EF, and LV force (systolic blood pressure + LVOTG/LV end-systolic volume assessed with 2-D, mmHg/mL). All patients were followed up. All-cause death was the outcome measure. Results At a median follow-up of 83 months, 150 deaths occurred (Group 1). At study entry, Group 1 patients had the same ESC-Sudden cardiac death score compared to survivors (Group 2). In Group 1 compared to Group 2, TTE showed higher values of MR severity, E/e’ , left atrial volume index, estimated systolic pulmonary artery pressure, and force (see table). At multivariable Cox analysis, only age (HR =1.08, 95% CI=1.03-1.14, p=0.001) and force > median value of 5.3 mmHg/mL (HR = 2.14, 95% CI 1.53-2.99, p=0.020) were independent predictors of mortality. Ten-year survival was 95% in the pooled first (<3.8 mmHg/mL) and second (3.8-5.2 mmHg/mL) quartiles vs 80% in the pooled third (5.3-7.8 mmHg/mL) and fourth quartiles (>7.8 mmHg/mL), see figure. Conclusion HCM patients with higher values of resting LV elastance show a worse survival, highlighting the dark prognostic side of an excess of force in these patients. Table Legends E/e’, early mitral inflow to early mitral annulus motion ratio, EF, left ventricular ejection fraction, LAVI, left atrial volume index; LVOTG, left ventricular outflow tract peak gradient, MR, mitral regurgitation; MWT, maximal wall thickness, NYHA, New York Heart Association classification, RWT, relative wall thickness; SCD risk, risk score for sudden cardiac death in hypertrophic cardiomyopathy, SPAP, systolic pulmonary arterial pressure.Table.Clinical and TTE findingsFigure.Survival in the force quartiles

Advances in risk assessment models for sudden cardiac death in hypertrophic cardiomyopathy

Advances in risk assessment models for sudden cardiac death in hypertrophic cardiomyopathy

Risk assessment and prevention of sudden cardiac death in hypertrophic cardiomyopathy

Risk assessment and prevention of sudden cardiac death in hypertrophic cardiomyopathy

Left atrial and left ventricular strain in feature-tracking cardiac magnetic resonance for predicting patients at high risk of sudden cardiac death in hypertrophic cardiomyopathy.

Sudden cardiac death (SCD) represents the most severe complication of hypertrophic cardiomyopathy (HCM). The risk stratification of SCD in patients with HCM remains a subject of ongoing debate, and the utility of left atrial (LA) and left ventricular (LV) myocardial strain for risk stratification of also SCD remains uncertain. Through use of feature-tracking cardiac magnetic resonance (FT-CMR), this study aimed to investigate the attenuation of LA and LV strain in HCM and to assess their predictive value in SCD. This retrospective and cross-sectional study included patients with HCM who underwent 3.0 T cardiac magnetic resonance (CMR) at a single institution. Feature-tracking strain analysis was conducted to obtain the strain rate (SR) and LV strain and to evaluate LV function. LA strain was measured during different functional phases including left atrial reservoir strain (LARS), LA conduit strain (LACS), and LA booster strain. All patients were categorized into high- and low-risk groups for SCD as defined by the 2020 American Heart Association/American College HCM implantable cardioverter defibrillator class of recommendation algorithm. Comparison between the two groups was conducted using the independent samples t test and the nonparametric rank sum test. Multivariate logistic regression analysis was performed to further identify the factors influencing SCD risk in HCM. Compared with those in the low-risk group, patients in the high-risk group had lower left ventricular ejection fraction (LVEF), LV stroke volume index (LVSVI), and LA stroke volume index (LASVI) but a higher LV end-systolic volume index (LVESVI), LV maximum wall thickness, and late gadolinium enhancement (LGE) (P<0.001). LV strain, SR, and LA strain all showed significant differences between the high- and low-risk groups (LARS: P=0.04; LACS: P=0.02; all other P values <0.001). The LV global circumferential strain (LVGCS) had a strong negative correlation with LVEF in patients with HCM (r=-0.76; P<0.001). Multivariate analysis showed that LV global radial strain (LVGRS) and LARS could be used for categorizing the patients into the high-risk group [LVGRS: odds ratio (OR) =0.69; 95% confidence interval (CI): 0.55-0.87, P<0.001; LARS: OR =1.39; 95% CI: 1.02-1.90, P=0.03]. The combined LVGRS-LARS model exhibited a superior diagnostic value for high risk of SCD [area under the curve (AUC) =0.95; 95% CI: 0.90-1.00; P<0.001] compared to LARS alone (AUC =0.63; 95% CI: 0.51-0.76; P=0.04). LA and LV strain measured by FT-CMR can accurately identify those patients with HCM at a high risk of SCD. This approach may prove considerably value in guiding early therapeutic intervention with implantable cardioverter-defibrillators (ICDs) to prevent adverse clinical outcomes.

An In Silico Cardiomyocyte Reveals the Impact of Changes in CaMKII Signalling on Cardiomyocyte Contraction Kinetics in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias, and cardiomyocyte dysfunction that may cause sudden death. HCM is associated with mutations in sarcomeric proteins and is usually transmitted as an autosomal-dominant trait. The aim of this in silico study was to assess the mechanisms that underlie the altered electrophysiological activity, contractility, regulation of energy metabolism, and crossbridge cycling in HCM at the single-cell level. To investigate this, we developed a human ventricular cardiomyocyte model that incorporates electrophysiology, metabolism, and force generation. The model was validated by its ability to reproduce the experimentally observed kinetic properties of human HCM induced by (a) remodelling of several ion channels and Ca2+-handling proteins arising from altered Ca2+/calmodulin kinase II signalling pathways and (b) increased Ca2+ sensitivity of the myofilament proteins. Our simulation showed a decreased phosphocreatine-to-ATP ratio (-9%) suggesting a negative mismatch between energy expenditure and supply. Using a spatial myofilament half-sarcomere model, we also compared the fraction of detached, weakly bound, and strongly bound crossbridges in the control and HCM conditions. Our simulations showed that HCM has more crossbridges in force-producing states than in the control condition. In conclusion, our model reveals that impaired crossbridge kinetics is accompanied by a negative mismatch between the ATP supply and demand ratio. This suggests that improving this ratio may reduce the incidence of sudden death in HCM.

Kiosk 5R-FB-07 - Left Atrial Strain Assessed by Cardiac MRI Improves Risk Stratification of Sudden Cardiac Death in Hypertrophic Cardiomyopathy

Kiosk 5R-FB-07 - Left Atrial Strain Assessed by Cardiac MRI Improves Risk Stratification of Sudden Cardiac Death in Hypertrophic Cardiomyopathy

Remote monitoring of cardiac implantable devices in children: characteristics and outcome in a retrospective single centre contemporary study. TelePaedia study

Abstract Introduction Remote monitoring (RM) has revolutionized implantable cardiac device care in adults. It has demonstrated its safety on hard criteria, a reduction in the number of hospitalizations and emergency room visits, early detection of events and a reduction in inappropriate therapies. However, while pediatric population is becoming emerging, particularly considering congenital heart diseases, there is no contemporary study. Objective The aim of our study was to characterize in our cohort of RM patients the population of children (below 18 yo) implanted with a pacemaker or an ICD and under RM for more than 1 year. Method The data collection was carried out retrospectively within the cohort of RM patients at our university hospital. The outcome combined occurrence of ventricular (VT)/supraventricular (SVT) arrhythmias, appropriate or inappropriate therapies, lead dysfunction/fracture and ERI. Results The study population included 34 patients (17F/17M) with a mean age of 9.4+/-5.8 years (range 0-18 yo) and a mean remote follow-up of 4.6+/-3.9 years (range 1-13 y). The indications for pacing were postoperative atrioventricular block (AVB, n = 9) for operated congenital heart disease or hypertrophic cardiomyopathy (n=1), congenital AVB (n= 5), muscular dystrophy (n = 1) and genetic sinus node dysfunction (n = 1). Indications for an ICD were resuscitated sudden death in hypertrophic cardiomyopathy (n = 4), LQTS (n = 5), CPVT (n = 2), arrhythmogenic right ventricular dysplasia (n = 2), Brugada syndrome (n = 1) and congenital heart disease (n = 2). Pacing devices (n = 17) were mostly implanted with epicardial leads and abdominal box (n = 12). ICDs (n = 18) were implanted in primary (n = 4) or in secondary prevention with epicardial (n = 2)/ endovascular (n=9) /subcutaneous (n = 2) leads depending on children weight and anatomy. One 12 yo-boy had an S-ICD in addition to a previous pacemaker. There were a total of 13 patients with device-triggered alerts: VT in 8 including appropriate therapies in 6 and inappropriate shocks in 2, supraventricular tachycardia in 2, RV lead dysfunction in 2, RV lead fracture in 1 and no alert for ERI. All alerts were treated within 24h. Conclusion This is the first report of cardiac device remote monitoring in a pediatric population. In our population 13/34 patients experienced alerts necessitating intervention over a mean 4.6 year-follow-up. Remote monitoring through device-triggered alerts allowed efficient treatment of an arrhythmic event or a lead dysfunction. This is a preliminary study suggesting the need for further studies on a larger population. Remote monitoring should be considered in all eligible-device children and should be considered as standard of care.

Late gadolinium enhancement entropy as a new measure of myocardial tissue heterogeneity for prediction of adverse cardiac events in patients with hypertrophic cardiomyopathy

ObjectivesEntropy is a new late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR)–derived parameter that is independent of signal intensity thresholds. Entropy can be used to measure myocardial tissue heterogeneity by comparing full pixel points of tissue images. This study investigated the incremental prognostic value of left ventricular (LV) entropy in patients with hypertrophic cardiomyopathy (HCM).MethodsThis study enrolled 337 participants with HCM who underwent 3.0-T CMR. The LV entropy was obtained by calculating the probability distribution of the LV myocardial pixel signal intensities of the LGE sequence. Patients who underwent CMR imaging were followed up for endpoints. The primary endpoint was defined as readmission to the hospital owing to heart failure. The secondary endpoint was the composite of the primary endpoint, sudden cardiac death and non-cardiovascular death.ResultsDuring the median follow-up of 24 months ± 13 (standard deviation), 43 patients who reached the primary and secondary endpoints had a higher entropy (6.20 ± 0.45, p < 0.001). The patients with increased entropy (≥ 5.587) had a higher risk of the primary and secondary endpoints, compared with HCM patients with low entropy (p < 0.001 for both). In addition, Cox analysis showed that LV entropy provided significant prognostic value for predicting both primary and secondary endpoints (HR: 1.291 and 1.273, all p < 0.001). Addition of LV entropy to the multivariable model improved model performance and risk reclassification (p < 0.05).ConclusionLV entropy assessed by CMR was an independent predictor of primary and secondary endpoints. LV entropy assessment contributes to improved risk stratification in patients with HCM.Critical relevance statementMyocardial heterogeneity reflected by entropy the derived parameter of LGE has prognostic value for adverse events in HCM. The measurement of LV entropy helped to identify patients with HCM who were at risk for heart failure and sudden cardiac death.Key points• Left ventricular entropy can reflect myocardial heterogeneity in HCM patients.• Left ventricular entropy was significantly higher in HCM patients who reached endpoint events.• Left ventricular entropy helps to predict the occurrence of heart failure and death in HCM patients.Graphical

Myocardial deformation as a stratification tool in HCM

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Sudden cardiac death (SCD) is a major issue in hypertrophic cardiomyopathy (HCM) management, and its risk prediction stays challenging for clinicians. Ventricular arrythmias (VAs) have to be treated rapidly, indeed VAs lower prognosis in HCM patients. Current ESC guidelines for cardioverter-defibrillator implantation include left atrial (LA) whereas left ventricle (LV) ejection function (LVEF) is incorporated in AHA latest guidelines. We explore the potential role of LA and LV strain as more sensible parameters in HCM rhythmic prognostication. Purpose To assess LA and LV strain in risk stratification in HCM patients as accurate markers of SCD. Methods Patients with newly diagnosed HCM were enrolled in three French University Hospital (Marseille, Bordeaux and Rennes) between 2007 and 2018. At the inclusion we realized a comprehensive clinical exam, biological analysis, an echocardiography including LA strain in two and four apical-chambers, and a MRI. Composite primary endpoint (PE) analysis was occurrence of rhythmic related adverse cardiac events: ventricular tachycardia (VT), ICD therapy for ventricular arrhythmia, or all-cause death. Occurrence and dates of endpoints were retrieved by patient’s medical records and phone calls to all patients and family members. Results At a mean follow-up of 57 (34–82) months, patients with adverse cardiac events (n = 52) presented with more impaired LA and LV deformation function. After multivariate analysis, we found a significant association between impaired LA strain and our composite primary endpoint P 0,023 HR 0,95. LV strain revealed to be correlated with our PE P 0,012 HR 2,48. Conclusions Myocardial deformation appears to be a relevant marker which could be linked to sudden cardiac death in HCM. These parameters might be relevant in new risk calculators.

Lifetime Clinical Course of Hypertrophic Cardiomyopathy: Outcome of the Historical Florence Cohort Over 5 Decades

BackgroundThe current understanding of the clinical course and long-term outcome of patients with hypertrophic cardiomyopathy (HCM) has been extrapolated from cohorts with relatively short follow-up, usually <10 years. Extended assessments more closely reflecting HCM lifetime burden are not available. ObjectivesThe purpose of this study was to report the lifetime clinical course of HCM. MethodsWe analyzed the clinical course of HCM patients diagnosed at our center from 1970 to 1992 and followed annually to the present. Cumulative incidence functions were used to estimate the incidence of HCM-related mortality (including heart failure [HF]/stroke related, sudden cardiac death [SCD]) and non-HCM related. ResultsA total of 202 patients (age 41 ± 17 years; 63% male) were followed 27 ± 6 [range: 3-50] years. Overall, 97 (48%) survived and 105 (52%) died during the particularly long follow-up; 69 deaths were related to HCM, including 53 HF related, 11 fatal embolic strokes, and 16 SCDs. Annual overall HCM-related mortality was 1.3%/y, increasing from 0.7% during the first decade to 1.8% in the second/third decade (P < 0.01), mainly driven by increase in HF-/stroke-related events (from 0.6% to 1.3%). The SCD mortality rate was similar in the 2 periods (0.1% vs 0.44%, P = 0.10). Of the 69 HCM deaths, 29 (42%) occurred before the widespread availability of effective contemporary treatment strategies and are considered potentially preventable. ConclusionsIn this unique HCM cohort followed for up to 50 years, often before contemporary therapies became widely implemented for HCM, HF frequently progressed over time, while arrhythmic SCD events were less common and remained constant over time. Despite spanning different management eras over 5 decades, HCM-related mortality remained relatively low (1.3%/y).

Solving the Riddle of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: The Added Role of Cardiac Magnetic Resonance

Cardiac magnetic resonance (CMR) has been recently implemented in clinical practice to refine the daunting task of establishing the risk of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We present an exemplificative case highlighting the practical clinical utility of this imaging modality in a 24-year-old man newly diagnosed with an apical HCM. CMR was essential in unmasking a high risk of SCD, which appeared low-intermediate after traditional risk assessment. A discussion examines the essential role of CMR in guiding the patient’s therapy and underlines the added value of CMR, including novel and potential CMR parameters, compared to traditional imaging assessment for SCD risk stratification.

Contribution of artificial intelligence and left atrial strain in the prediction of sudden cardiac death in hypertrophic cardiomyopathy. Results of a multicentric cohort

Sudden cardiac death (SCD) remains a serious outcome in hypertrophic cardiomyopathy (HCM), with an estimated incidence of 1%/year. Its risk prediction stays challenging for clinicians. Implantation of cardioverter-defibrillator is recommended with a strong level of evidence when the HCM risk score is over 6%. However, the ESC HCM risk score is criticized for its moderate diagnostic performance (C-index 0,70), and its low sensibility. Recent studies suggest that low PALS (peak atrial longitudinal strain) is associated with poor prognosis in HCM. Artificial intelligence, wich is experiencing an unprecedented boom, may be an interesting tool in association to left atrial strain in Prognostication. This preliminar study aimed to evaluate the value of the left atrial strain coupled with artificial inteligence algorythm in the prediction of suddent cardiac death in hypertrophic cardiomyopathy. This restrospective multi-center cohort (Marseille la Timone, Bordeaux and Rennes) included 431 patients with sarcomeric HCM from 2007 to 2018. The average follow-up time was 57 months. The primary endpoint was all cause death, ventricular arythmias, recovered SCD and internal electric shock. Analyses were entrusted to the LIS laboratory specialized in Computer Science at Aix-Marseille University. Sixty-six percent of men composed the cohort with a mean age of 52 ± 16 yo. Sarcomeric mutations were found in 52% of them, the mean left ventricular ejection fraction was 63 ± 16, 23% had significant ventricular obstruction. The mean PALS was 25 ± 12%. In the multivariate analysis, PALS 4 chamber, left ventricular global longitudinal strain and syncope were associated with the primary endpoint, (respectivly HR 2,48 IC95% [1,09–5,63]; P 0,030; HR 1,13 IC95% [1,03–1,25]; P 0,012; HR 0,95 IC95% [0,92–0,99]; P: 0.023). The random Forrest algorithm was able to successfully classify the patient (occurrence of primary endpoint or not) in 92,2% of the cases. Left atrial strain coupled with the Random Forrest algorithm could offer an interesting implementative value for the prediction of sudden cardiac death in hypertrophic cardiomyopathy. Further analysis are required to define its sensibility and specificity.

Do apical aneurysms predict sudden cardiac death in hypertrophic cardiomyopathy?

The current AHA/ACC HCM guideline recommendation for a primary prevention ICD is based on retrospective series that have important limitations. These include selection bias, the fact that ‘SCD events’ are appropriate ICD interventions for monomorphic VT in the vast majority of cases, and a high prevalence of major confounders in patients with apical aneurysm and SCD events. HCM, hypertrophic cardiomyopathy; SCD, sudden cardiac death; LV, left ventricular; LVEF, left ventricular ejection fraction; VF, ventricular fibrillation; VT, ventricular tachycardia (Lorenzini et al. 2020). Lorenzini M et al. Mortality Among Referral Patients With Hypertrophic Cardiomyopathy vs. the General European Population. JAMA Cardiology 2020; 5:73–80.

Abstract 14304: Does QRS Fragmentation Have a Role in Risk Stratification for Sudden Death in Hypertrophic Cardiomyopathy?

Background: Fragmentation of the QRS complex on 12-lead electrocardiogram (ECG) represents alterations of myocardial activation due to myocardial scarring and has been associated with increased risk for sudden death and adverse prognosis. However the clinical significance of this finding in hypertrophic cardiomyopathy (HCM) remains unresolved. Methods: Consecutive HCM patients evaluated from 2004 to 2020 were included and followed for 5.1 ± 4.1 years for outcomes including sudden death events (appropriate ICD interventions for VT/VF, cardiac arrest, or sudden death) and development of endstage heart failure requiring transplant. QRS fragmentation was defined as presence of an additional R wave or notching in the R or S wave in two contiguous ECG leads in the absence of bundle branch block. Results: Among 1929 HCM patients, 539 (28%) were identified with QRS fragmentation. As compared to patients without QRS fragmentation, patients with QRS fragmentation had similar baseline demographics including age (52±16 vs. 53±16, p=0.35), gender (60% vs. 61% male, p=0.51), ejection fraction (64 ± 6 vs. 64 ± 5, p=0.77) and presence of LV outflow obstruction (≥30mmHg at rest or provocation; 65% vs. 65%, p=0.9). While patients with QRS fragmentation had more substantial LV hypertrophy (19 ± 4 vs. 18 ± 4, p=0.001) as well as presence and extent of late gadolinium enhancement by cardiac MRI (64% vs. 56%, 6.3 ± 6 vs. 5 ± 5, p&lt;0.01), there was no difference in other risk markers including syncope (9% vs 9%, p=0.89), family history of SD (8% vs. 6%, p=0.31), NSVT (10.5% vs. 8%, p=0.10). Over follow-up, patients with QRS fragmentation were at increased risk for sudden death events (5.6% vs. 2.2%, p&lt;0.001) and development of end-stage heart failure requiring transplant (2.4% vs. 0.8%, p=0.007). However, sensitivity and positive predictive value of QRS fragmentation for predicting sudden death events (50% and 5.6%, respectively) as well as endstage heart failure (52% and 2.4%) is limited. Conclusion: In a large consecutive HCM cohort, QRS fragmentation on 12-lead ECG is associated with extreme HCM phenotype and a number of adverse consequences including sudden death events and endstage development, and represents a potential prognostic marker.

Myocardial Activity at 18F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Background Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relationship with the risk of sudden cardiac death (SCD) in HCM. Materials and Methods In this prospective study from July 2021 to January 2022, participants with HCM and healthy control participants underwent cardiac fluorine 18 (18F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV × target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable linear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results Fifty study participants with HCM (mean age, 43 years ± 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years ± 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respectively; P < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; P < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed N-terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diameter and a negative relationship with LV ejection fraction z-score. Degree of FAPI activity positively correlated with the 5-year SCD risk score (r = 0.32; P = .03). Conclusion Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hypertrophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death. © RSNA, 2022 Online supplemental material is available for this article.

Symptoms and ECG changes precede sudden cardiac death in hypertrophic cardiomyopathy-A nationwide study among the young in Sweden.

BackgroundHypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death (SCD) in the young. We aimed to characterize detailed family history, symptoms, hospital utilization and ECG changes before SCD.MethodsWe extracted all cases suffering SCD with HCM from the SUDDY cohort, which includes all cases of SCD between 2000–2010 in Sweden among individuals aged 0–35 years along with their controls. We gathered data from mandatory national registries, autopsy reports, medical records, ECGs (including military conscripts), and detailed family history from an interview-based questionnaire (with relatives, post-mortem).ResultsThirty-eight cases (7 female), mean age 22 years, with HCM were identified. Among these, 71% presented with possible cardiac symptoms (chest pain [26%], syncope [22%], palpitations [37%]), before death; 69% received medical care (vs 21% in controls) within 180 days before death. The majority (68%) died during recreational activity (n = 14) or exercise/competitive sports (n = 12). Fifteen (39%) had a known cardiac disorder prior to death, with HCM being diagnosed pre-mortem in nine cases. 58% presented with abnormal ECG recordings pre-mortem, and 50% had a positive family history (1st-3rd generation) for heart disease.ConclusionIn this comprehensive, nationwide study of SCD due to HCM, 87% (33/38) of cases had one or more abnormality prior to death, including cardiac symptoms, a positive family history, known cardiac disease or ECG abnormalities. They sought medical care prior death, to a larger extent than controls. These findings suggest that cardiac screening should be expanded beyond competitive athletes to aid SCD prevention in the young population with HCM.

Ventricular arrhythmia and sudden cardiac death in hypertrophic cardiomyopathy: From bench to bedside.

Patients with hypertrophic cardiomyopathy (HCM) mostly experience minimal symptoms throughout their lifetime, and some individuals have an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). How to identify patients with a higher risk of ventricular arrythmias and SCD is the priority in HCM research. The American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) both recommend the use of risk algorithms to identify patients at high risk of ventricular arrhythmias, to be selected for implantation of implantable cardioverters/defibrillators (ICDs) for primary prevention of SCD, although major discrepancies exist. The present SCD risk scoring systems cannot accurately identify early-stage HCM patients with modest structural remodeling and mild disease manifestations. Unfortunately, SCD events could occur in young asymptomatic HCM patients and even as initial symptoms, prompting the determination of new risk factors for SCD. This review summarizes the studies based on patients' surgical specimens, transgenic animals, and patient-derived induced pluripotent stem cells (hiPSCs) to explore the possible molecular mechanism of ventricular arrhythmia and SCD. Ion channel remodeling, Ca2+ homeostasis abnormalities, and increased myofilament Ca2+ sensitivity may contribute to changes in action potential duration (APD), reentry circuit formation, and trigger activities, such as early aferdepolarization (EAD) or delayed afterdepolarization (DAD), leading to ventricular arrhythmia in HCM. Besides the ICD implantation, novel drugs represented by the late sodium current channel inhibitor and myosin inhibitor also shed light on the prevention of HCM-related arrhythmias. The ideal prevention strategy of SCD in early-stage HCM patients needs to be combined with gene screening, hiPSC-CM testing, machine learning, and advanced ECG studies, thus achieving individualized SCD prevention.

PO-716-05 VENTRICULAR REPOLARIZATION IN CARDIAC AMYLOIDOSIS

Despite a high incidence of non-sustained ventricular tachycardia in patients with transthyretin cardiac amyloidosis (TTR-CA), sudden tachyarrhythmic death is uncommon. Homogeneous myocardial deposition of amyloid fibrils may mitigate against sustained ventricular arrhythmias. In contrast, myocardial scar heterogeneity is an established predictor of sudden cardiac death in hypertrophic cardiomyopathy (HCM), as evidenced by increased myocardial dispersion of repolarization. Whether such indices of arrhythmogenesis are evident in TTR-CA has not been established.

Impact of comorbidities on atrial fibrillation and sudden cardiac death in hypertrophic cardiomyopathy.

The impact of comorbid disease states on the development of atrial and ventricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) remains unresolved. Evaluate the association of comorbidities linked to arrhythmias in other cardiovascular diseases (e.g., obesity, systemic hypertension, diabetes, obstructive sleep apnea, renal disorders, tobacco, and alcohol use) to atrial fibrillation (AF) and sudden cardiac death (SCD) events in a large cohort of HCM patients. A total of 2269 patients, 54 ± 15 years of age, 1392 males, were evaluated at the Tufts HCM Institute between 2004 and 2018 and followed for an average of 4 ± 3 years for new-onset clinical AF and SCD events (appropriate defibrillation for ventricular tachyarrhythmias, resuscitated cardiac arrest, or SCD). One or more comorbidity was present in 75% of HCM patients, including 50% with ≥2 comorbidities, most commonly obesity (body mass index [BMI] ≥ 30 kg/m2 ) in 43%. New-onset atrial fibrillation developed in 11% of our cohort (2.6%/year). On univariate analysis, obesity was associated with a 1.7-fold increased risk for AF (p = .03) with 12% of obese patients developing AF (3.3%/year) as compared to 7% of patients with BMI < 25 kg/m2 (1.6%/year; p = .006). On multivariate analysis, age and LA transverse dimension emerged as the only variables predictive of AF. Comorbidities, including obesity, were not independently associated with AF development (p > .10 for each). SCD events occurred in 3.3% of patients (0.8%/year) and neither obesity nor other comorbidities were associated with increased risk for SCD (p > .10 for each). In adult HCM patients comorbidities do not appear to impact AF or SCD risk. Therefore, for most patients with HCM, adverse disease related events of AF and SCD appear to be primarily driven by underlying left ventricular and atrial myopathy as opposed to comorbidities.

Risk factors of sudden cardiac death in hypertrophic cardiomyopathy.

Purpose of reviewHypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death (SCD) in younger people and athletes. It is crucial to identify the risk factors for SCD in individuals with HCM. This review, based on recent systematic literature studies, will focus on the risk factors for SCD in patients with HCM.Recent findingsAn increasing number of studies have further explored the risk factors for SCD in patients with HCM, and new risk markers have emerged accordingly. In addition, more accurate SCD risk estimation and stratification methods have been proposed and continuously improved.SummaryThe identification of independent risk factors for HCM-related SCD would likely contribute to risk stratification. However, it is difficult to predict SCD with absolute certainty, as the annual incidence of SCD in adult patients with HCM is approximately 1%. The review discusses the established risk factors, such as a family history of SCD, unexplained syncope and some new risk factors. Taken together, the findings of this review demonstrate that there is a need for further research on individual risk factors and that SCD risk stratification in HCM patients remains a clinical challenge.